Postischemic acute renal failure (ARF) is influenced by gender. Na+/K+-ATPase (NKA) plays a crucial role in the pathogenesis of postischemic ARF. We tested the impact of gender on mRNA, protein expression, cellular distribution and enzyme activity of NKA following renal ischemia/reperfusion (I/R) injury. The left renal pedicle of uninephrectomized female (F) and male (M) Wistar rats was clamped for 55 minutes followed by 2 (T2) and 16 (T16) hours of reperfusion. Uninephrectomized, sham-operated F and M rats served as controls (n=6/group). Blood urea nitrogen (BUN), serum creatinine, sodium, potassium levels and renal histology were evaluated to detect the severity of postischemic ARF. mRNA expression of NKA 1 and ß1 subunits were detected by RT-PCR. The effect of I/R on cellular distribution was compared by Triton X-100 extraction. Cellular proteins were divided into Triton-insoluble and Triton-soluble fractions and assessed by Western blot. NKA enzyme activity was also determined. After the ischemic insult BUN, serum creatinine and potassium levels were higher and renal histology showed more rapid progression in M vs. F (P<0.05). mRNA expression of NKA 1 subunit decreased in I/R groups vs. controls, but was higher in F vs. M both in control and I/R group (P<0.05). However protein levels of NKA 1 subunit in total tissue homogenate did not differ in controls, but were higher in F vs. M at I/R groups (P<0.05). Triton X-100 extractability was lower in F vs. M at T16 (P<0.05). NKA enzyme activity was the same in controls, but was higher in F vs. M in I/R groups (T2: 14.9±2.3U vs. 9.15±2.21U) (T16: 11.7±4.1U vs. 5.65±2.3U; P<0.05). mRNA and protein expression of NKA ß1 subunit did not differ between females and males in any of the protocol. We concluded that NKA is more protected from detrimental effects of postischemic injury in females. Higher mRNA and protein expression of NKA 1 subunit and higher enzyme activity might be additional contributing factors of improved postischemic renal function of female rats.