The present study aimed to assess some biochemical changes of oxidative stress in alloxaninduced diabetic rats with administration of lipoic acid. The experiment was carried out on 96 male rats. The group I (32 rats) was left as control (normal non-diabetic). Sixty-four rats were injected subcutaneously with alloxan (120 mg / kg.b.wt.) for induction of diabetes. Then it was divided into two equal groups, group II (diabetic without administration of lipoic acid) and group III (diabetic with administration of lipoic acid). Blood samples were collected from 8 rats of each group for separation of clear serum at 1st, 2nd, 3rd and the 4th week after administration for determination of glucose. Fresh liver and brain tissue samples (0.2 g) were collected from sacrificed rats and homogenized in ten volumes of (ice-cold phosphate saline pH: 7), then kept at –20 ?C for assay of malondialdehyde, reduced glutathione and liver glycogen. The obtained data revealed that serum glucose level was significantly decreased in the 3rd group as compared with the diabetic one. Also there was a significant decrease of liver glycogen in the diabetic group as compared with the non-diabetic control group. Moreover, significant decrease of reduced glutathione in both liver and brain tissues in diabetic group as compared with control. Lipoic acid caused a significant elevation in liver reduced glutathione as compared with the diabetic group, but without effect on brain. There was a significant rise in malondialdehyde in liver and brain tissues of diabetic group as compared with control. On the other hand there was a significant decrease of malondialdehyde in liver and brain tissues of diabetic rats with lipoic acid as compared with diabetic rats throughout the experiment period. It could be concluded that significant increase of malondialdehyde together with the decrease of reduced glutathione in the diabetic group: indicated the oxidative stress of induced diabetes. Also the study revealed that lipoic acid exerted a powerful antioxidant effect and therefore the diabetics should be supplemented regularly with this vitamin.