Caffeine is one of the most widely consumed as well as pharmacologically active ingredient in the world. Traditionally use of caffeine has increased substantially as many caffeinated drinks are being consumed. The main effects of caffeine are anxiety, fast heartbeat, restlessness, insomonia and dehydration. The present study analysed the histology of liver and effect on blood microflora of albino rats. The liver plays an essential role in metabolism and produces digestive enzymes stores bile produce hormones and remove toxins. Three doses were tested to observe histological changes in microflora of blood of animals, they were 3 mg/5ml distilled water; 6 mg/5 ml distilled water and 9 mg/5ml and extreme dose of 125 mg/5 ml distilled water. Untreated rats were kept as control. There were three replicates of each treatment. In animals treated with 3 mg/5 ml of distilled water showed rounded hepatocytes with ill-defined cell walls. Transverse section of liver treated with 6 mg/5 ml of distilled water showed rounded occlusion of central vein with deformed RBC’s and leucocytes, most macrophages had empty spaces at the site of central vein, while in the acute dose of caffeine thrombosis of blood vessels, aggregation of platelets, bound together by erythrocytes and fibrin. The leucocytes were visible in large blood vessel. Nuclei of hepatocytes disappeared while in the untreated albino rats the liver tissue was normal. While 9 mg/ 5 ml distilled water showed thrombosis, aggregation of platelets bound together by fibrin, while acute dose revealed degeneration of hepatic cells. Endothelial cells were abnormally enlarged and necrosis.A regular blood culture was done to detect any becteremia. Blood cultures of treated and untreated animals were tested. Blood of treated and untreated albino rats did not reveal the presence of bacteria i.e. no bacteremia.