The present study was conducted to evaluate the effect of glibenclamide and metformin on some biochemical parameters in rats induced epilepsy. Male Wister was induced epilepsy by injection of pentylenetetrazole (PTZ) at a dose 100 mg/kg of body weight, the rats randomly divided into 3 groups (10-12 rat/group). The group 1: leaved without treatment and served as control group; Group 2: was treated with glibenclamide 5 mg/kg.b.w.; Group 3: was treated with metformin 150 mg/kg.b.w. All treatments were once daily for 1 week, blood samples were collected at 3, 24 hours, and week after induced of epilepsy. The results show that treated with PTZ leads to significant decrease in glucose level in all times after treatment, and significantly decreased level of cholesterol after 3 hours, and a week after treatment, while level of albumin was significantly decreased after a week of treatment, also PTZ treatment increased level of aspartate aminotransferase (AST) in all times after treatment, while level of alanine aminotransferase (ALT) was significantly increased after 3 hours, then significantly decreased after a week of treatment. PTZ treatment doesn't show any effect on levels of total protein, and globulin. Treatment with glibenclamide leads to significant increase level of glucose in all times after treatment, also level of cholesterol was significantly increased at 3, 24 hours after treatment with glibenclamide. Level of (AST) was significantly decreased in all times after treatment with glibenclamide, but level of (ALT) was increased only after a week of treatment, glibenclamide don't cause any effect on levels total protein, albumin, and globulin. Treatment with metformin leads to significantly decreased level of glucose after 3, 24 hours of treatment, with significant increase after a week of treatment, while level of cholesterol was significantly increased after 3 hours, and significantly decreased after 24 hours of treatment. Levels of total protein and globulin were increased significantly after 3 hours only, level of albumin significant decrease after 24 hours treatment, also metformin lead to significantly decreased level of (AST) after 3 hours, and significantly increased after a week of treatment, while (ALT) level significantly increased after 24 hour, and week of treatment. These results indicate that glibenclamide and metformin have good roles in control of epilepsy-induced by PTZ in rats through several significant changes of biochemical parameters.