Purpose: We aimed to investigate the relationship between L-arginine-nitric oxide (NO) and L-arginine-asymmetric dimethylarginine (ADMA) pathways in kidney and liver during endotoxemia. Material and Methods: In the present study, twenty adult male guinea pigs were randomly divided into two groups; control and endotoxemia. Endotoxemia was induced by a single intraperitoneally injection of lipopolysaccharide (LPS, 4 mg/kg). After six hours of incubation, when highest blood level of endotoxin was attained, the animals were sacrificed, and kidney and liver tissue samples were collected. The amounts of ADMA and L-arginine were measured by HPLC, and arginase activity and levels of reactive nitrogen oxide species (NOx) which are stable end products of NO were measured spectrophotometrically. Results: LPS administration significantly decreased ADMA and L-arginine levels, and increased arginase activity and NOx levels compared to control group in liver. As for kidney, LPS administration significantly elevated ADMA levels and arginase activity, and decreased NOx levels compared with control group. But, L-arginine levels did not change in kidney during endotoxemia. Conclusion: It has been concluded that L-arginine-NO, L-arginine-ADMA pathways and arginase activity were important factors in endotoxin mediated liver and kidney tissue impairment. The changes observed in L-arginine-NO and L-arginine-ADMA pathways were opposite of each other during endotoxemia. We believed that this situation was the result of functional differences in these tissues.