Omeprazole is widely used in the treatment of the gastroesophageal reflux and peptic ulcer diseases. It inhibits the proton pump in the gastric parietal cells. Proton pumps also exist in kidney nephron. However, the renal effects of omeprazole have not been elucidated yet. T'his study investigates the effects of omeprazole intramuscular administration for four weeks on mean arterial pressure (MAP), renal blood flow Q{BF), renal vascular reactivity to both phenylephrine (PFIE) and dopamine (DA) and on tubular excretion. Kidneys were also examined for histopathological changes. The study inctuded four groups of rat (n:6), the secotta and the fourth served as control and were injected with the vehicle for 4 weeks. The first and the third were injected with omeprazole (0.2 mdkg) for the same time period. Chronic omperazole administration slightly reduced RBF (from 12.1*0.3 to 11.2t0.4 ml/min) but significantly reduced the responsiveness of the renal vasculature to the vasoconstrictor PFIE and the vasodilator DA. Urinary pH was increased (6.8 to 7 6) and urine flow rate was slightly decreased (from SOiO to f grs pl/min). Na+ and K* excretion was impaired (from ll0tll to 72+9 mmol/min for Na+ and from 69*6 to 47L7 mmol/min for K+). Albumin traces were detected in urine. Histopathological examination showed evidence of interstitial nephritis. Thus, chronic use of omeprazole may be associated with renal damage and impaired kidney functions.