The study was performed in to investigate the effects of butter and estrogen on lipid profile and histo-texture of liver and skin in mice. 30 days old 60 (30 male and 30 female) Swiss Albino mice were divided into 6 equal groups of which (M, M1, and M2) were in male and (F, F1, F2) in female. Group M and F (Control) were fed with normal mice pellet. Mice in the group M1 and F1 (butter treated) were fed with 20% butter; group M2 and F2 (estrogen) were fed with estrogen @ of 10 ?g/mice/day. The effect of butter and estrogen in the development of obesity in mice was evaluated based on weight gain, lipid profile, blood glucose and histopathology. In this study in case of male the highest body weight gain was detected in group M1 (P<0.001) and in biochemical study, group M1 showed the increase in total plasma cholesterol (P<0.01), LDL (P<0.01), TG (P<0.001), blood glucose (P<0.05) but increase in HDL (P<0.001) in M2 group compared to control group. In female the highest body weight gain was detected in group F1 (p<0.001) and in biochemical study, group F1 showed the increase in total plasma cholesterol (P<0.01), LDL (P<0.01), TG (P<0.001), blood glucose (P<0.05) but increase in HDL (P<0.001) in F2 group in compared to control group. In histopathological study fatty changes and endothelial desquamation were found in the liver of butter treated groups. Fatty changes, loss of elasticity, dermal thickness were found in the skin of butter treated mice. On the basis of the findings and observations of the present study, it can be concluded that 20% butter supplementation would be able to cause a change in lipid profile and would also produce degenerative changes in liver and skin of mice.