Abstract: Orexin-A and orexin-B are peptides produced specifically by neurones located in the lateral hypothalamus, a region involved in the central regulation of feeding behaviour. Recent studies documented the presence of orexins and orexin receptors in peripheral tissues e.g., in the kidney. Therefore we examined the influence of exogenous orexin-A and orexin-B on renal function. The natriuresis, diuresis and creatinine clearance were analysed after intraperitoneally administration of orexins. The study investigated the possible mechanism through which orexin affects renal sodium sparing. For this reason, we measured the Na+,K+-ATPase activity in renal cortex and medulla after locally infusion of orexin-A through the catheter inserted into the abdominal aorta close to the renal arteries. The study was performed on male Wistar rats. Orexin-A and orexin-B were given i.p. in two doses: 2nmol rat-1 or 10 nmol rat-1. The conscious animals were placed in metabolic cases and the urinary collection was made after 2 h of orexin-A or orexin-B administration. The intra-arterial infusion of orexin-A (66.7 or 333.3 pmol min-1) was performed 30 min on rats under anaesthesia. The urine to estimate diuresis and natriuresis was collected directly after the surgery. The Na+, K+-ATPase activity was assayed in an isolated microsomal fraction of the renal cortex and medulla. The i.p. administration of orexin-A caused the decrease in natriuresis and fractional sodium extraction without change in glomerular filtration rate (GRF) estimated by calculating creatinine clearance. Neither low or high dose of orexin-B had effect on renal function. The Na+,K+-ATPase activity was increased in renal cortex and medulla after infusion of orexin-A (333.3 pmol min-1) by 32.4 and 9.11%, respectively. These date indicate that orexin-A given i.p can affect the renal sodium retention, probably by activating tubular sodium reabsorption mediated via an increase of Na+, K+-ATPase activity.