The OBJECTIVE of the study was to create a model of acute hematogenous pyelonephritis in the rat without causing urinary retention by ligation of the ureter. Mixed bacterial suspension containing 1.5 x 10(6) colony-forming units (CFU) of S. aureus and 3.0 x 10(6) CFU of E. coli was inoculated in the caudal vein at a dose of 0.5 ml/kg. Control animals received the same amount of saline solution. Pyelonephritis was confirmed by lab urine tests and histopathological study of the kidneys. Infected animals initially developed sepsis with a significant increase of leukocytes and C-reactive protein in the blood. Originally only bacteriuria was found in the urine of experimental animals, but later, in the course of the development of pyelonephritis (12-18 days), leucocyturia and active leukocytes (glitter cells) were also available in urine. The levels of beta-2 microglobulin in the urine of infected animals (4.02 +/- 0.04 mmol/l on day 16 and 4.18 + 0.07 mmol/l on day 18) were significantly highly increased (p <0.0001) in comparison with the value of the control group (0.088 +/- 0.005 mmol/l). In the early days the histopathological examination of the kidneys established erythrocyte stasis. Later leukocyte infiltrates were observed in the interstitial tissue around the kidney tubules, glomeruli and vascular walls, and inflammatory cell infiltration and degenerative changes were present in the epithelium of the canaliculi. Combined hematogenous infection with S. aureus and E. coli led to the development of pyelonephritis in rats. The pathology in the kidney tubules was confirmed by histopathological study and by the elevated levels of beta-2 microglobulin and the presence of active leukocytes in urine.