Obesity is one of the common diseases of the era, which spread strongly in our life. The development of science led to the find out of many Drugs, the purpose of which was to find the optimal treatment to get rid of excess weight for humans, and through scientific follow-ups, it was seen that anti-obesity treatments (which are many types) It has many side effects, and in most cases, it appears suddenly without calculating the effect. In this research, the anti-obesity drug Orlistat was studied, done on 50 rats in which obesity was induced by feeding them high-fat Diet(HFD), where the rats were divided into five groups of 10 rats per group( 10=negative control group in 30 and 60 days),(10 positive control group were feeding HFD only in two periods 30 &60 days),(10= were oral administration with orlistat 50 mg /kg /day in two period 30 &60 days),(10= were oral administration with orlistat 100 mg /kg /day in two period 30 &60 days),( 10= were oral administration with orlistat 150 mg /kg /day in two period 30 &60 days).stuydied the initial body weight and final body weight,also in this present study examine the relative organ weight (liver) then examined the histological and physiological effect on liver as an important part of the body. Results revealed significant decrease in final body weight and relative weight of liver in treated rats with orlistat compared with negative control and (HFD)group, significant increase in Liver enzyme ,pathological change in the liver tissue necrosis and congestion of blood vessel, degeneration in hepatocyte ,results displayed that 60 days were more effect than 30 days and conc.150 mg/kg/day was more effected .