198 male albino rats were used in this experiment. First, 42 rats were divided into 13 different dietary groups to test the effects of high fat and cholesterol in the diet on the level of serum cholesterol and the degree of atherogenesis. Then the effects of four different types of diet upon the healing of small vessel anastomoses were studied. Group one received a regular control diet (MF diet, Oriental KOBO Co. Ltd.), group two, A diet (regular diet with cholesterol 5 % , peanut oil 5% and sodium cholate 2%), group three, AP diet (A diet with pyridinolcarbamate 0.05%), group four, AT diet (A diet with thiouracil 0.3%). All percentages were calculated on a weight basis. Each group received the above diets for 13 weeks before anastomosis. Then, end to end anastomosis of the common carotid artery was performed using the operating microscope. Rats were sacrificed in groups of 2 to 6 from 24 hours to 20 weeks postoperatively. Vessel patency was determined and histological and histochemical changes were noted. Average values of the level of s-cholesterol at the time of sacrifice were 80 mg/dl in the normal group, 484 mg/dl in the A group, 342 mg/dl in the AP group and 661 mg/dl in the AT group and patency rates were 23/30 (77%), 16/36 (44%), 17/32 (53%) and 3/8 (38%) respectively. Histologically, diffuse degeneration of smooth muscle cells in the media and marked deposition of fat granules in the intima and media were observed in the hypercholesteremic rats of groups A and AT. In the AT group mural thrombi were often observed around the site of anastomosis with narrowing of the lumen. In rats fed atherogenic diets, healing of the anastomosis was significantly delayed requiring 6 to 8 weeks as determined by histological evidence and about 12 weeks by histochemical. Some degree of degeneration with fat granules was noted in the walls of the vessels at the sites where the vascular clamps had been applied. Histochemical examination of anastomosed vessels from rats fed atherogenic diets A and AT showed markedly lower activities of LDH, G-6-PDH, SDH and Cy-O in the media and rather higher activities in the adventitia than in vessels from rats fed control diets. In all groups Ac-P activity increased in the adventitia following surgery then decreased gradually with the healing process and Al-P activity increased temporarily in granulation tissue. But the activity of this latter enzyme was found to be markedly decreased in the adventitia following surgery in the vessels of rats fed atherogenic diets and seemed to be correlated with the degree of medial necrosis. Patency rates were very low in rats fed the A, AP and AT diets as compared to those fed the control diet, there being a clear tendency for higher cholesterol levels to result in lower patency rates. It would appear that persistent hypercholesterolemia increases the risk of delayed occlusion at the anastomotic site caused by mural thrombi or atheromatous change. The rats in the AP group showed less prominent fat infiltration of the vessel wall and fewer mural thrombi than those of the A or AT groups. This work suggests that it would be advantageous to administer anti-coagulant and/or anti-atherogenic medication after vascular anastomosis and to maintain that therapy throughout the duration of the healing process.