The present study was carried out to evaluate the possible ameiolrative role of some compounds on the side effects  of Rosiglitazone. Nigella sativa, Silymarin each alone and the combination of Rosiglitazone with either Nigella sativa or Silymarin In order to get the best combination to avoid the possible side effects produced by Rosiglitazone. This was done through studying the effect of these plant extract and their combination on some lipid parameters and sex hormones .seven groups of adult male rats each of 10 (200-250 gm) were used in this study. Hyperglycemia was induced in six groups of rats. Whereas, the 7^th  group was left as normal control group. All treatments were given orally daily for successive 28 days The 1^st group was left without treatment and kept as STZ diabetic. The 2^nd group was administered Rosiglitazone (0.58mg/ 100gm). The 3^rd  group was given Nigella sativa (0.25gm/100gm) , the 4^th  group was given Silymarin (50mg/100gm). The 5^th  and 6^th  groups were administered the combination of Rosiglitazone with either Nigella sativa or Silymarin respectively in the same recommended doses. Blood samples were collected after 1st, 2nd, 3rd and 4th week post drug administration. Serum was separated and used for determination of various variables. The results showed that Rosiglitazone afforded a marked decrease in serum Triglycerides, Total cholesterol, LDL-c, VLDL-c levels as well as a slight to significant increase in serum HDL concentration along the course of the study and decreased testosterone hormone. Treatment of diabetic rats with various treatments elicited a marked decrease in serum Triglycerides. Total cholesterol, LDL-c, VLDL-c as well as a marked increase in serum HDL-c level when compared With diabetic non treated group and diabetic group treated with Rosiglitazone drug, the histopathological changes were also studied.