Background: In Egypt, gabapentin (GBP) misuse and abuse have been increased in the last decade after scheduling of its analogue pregabalin in 2012. Although many studies confirmed the deleterious effects of pregabalin, those of GBP are minimal. The aim of this research is to study and evaluate the nephrotoxic effects of sub chronic high dose administration of GBP and the protective effect of alpha-tocopherol. Methods: Thirty five (35) healthy male albino rats were included. They were randomly divided into; four groups: group I (15 rats) which were subdivided into group Ia (5 rats) negative control (normal diet), group Ib (5 rats) positve control (normal saline), group Ic (5 rats) positve control (Corn Oil), group II which were further subdivided into group IIa (5 rats) (GBP misuse), group IIb (5 rats) (GBP withdrawal), group ΙII (5 rats) (alpha-tocopherol) and group ΙV (5 rats) (GBP + alpha-tocopherol). All rats received the commenced drugs for 40 days. Serum levels of urea, creatinine and uric acid were measured. Kidney tissues were taken for histopathology. Results: GBP increased renal biomarkers levels, disrupted renal tissues and increased the number of degenerated cells. Alpha tocopherol treatment significantly attenuated the deleterious effects induced by GBP. Conclusions: High dose sub chronic administration of GBP was associated with nephrotoxic effects in rats. The histopathological effects were less appeared during withdrawal period. Alpha tocopherol protects against GBP induced impairment of kidney functions.