The present study was conducted to evaluate pathophysiological alterations after repeated oral administration of marbofloxacin alone and along with piperine pretreatment in rats. Blood samples were collected from treated animals at 6 th day. Hematological parameters (Hb, PCV, TLC, TEC, DLC, MCV, MCH and MCHC) and serum biochemical parameters (ALT, AST, total protein, albumin, globulin, LDH, creatinine, BUN, bilirubin and AKP) were estimated after five days treatment. Hematological and serum biochemical parameters were not found influenced after treatments and their mean values were not significantly altered (p>0.01) from corresponding control values. Moreover, no gross or microscopic changes were found in all major organs except liver of the treated rats. The histopathological changes in liver of treatment groups II (marbofloxacin alone) and III (marbofloxacin with piperine pretreatment) revealed mild degree of congestion and vacuolar degeneration in hepatocytes. It was concluded that piperine pretreatment for 5 th day in rats did not produce significant pathophysiological alterations in blood, serum biochemical parameters and microscopic changes in major organs with absence of clinical signs of side effects, following repeated oral administration of marbofloxacin.