Background and Aim: Spontaneous bacterial peritonitis (SBP) is a prototypical infectious disease prevailing in patients with cirrhosis and ascites requiring speedy recognition and treatment. Once infection develops, proinflammatory and anti-inflammatory cytokines as (IL-10) are released to blood and ascites. This study aimed to evaluate the changes in serum and ascitic levels of Interleukin-10 in cirrhotic patients with spontaneous bacterial peritonitis to detect its role in diagnosis and/or pathogenesis of SBP. Patients and Methods: We prospectively observed 65 subjects admitted in Hepatology, Gastroentrology and Infectious diseases Department, Benha university The subjects were categorized into three groups; group I included 20 healthy subjects (control group), group II included 20 cirrhotic patients without SBP and group III included 25 cirrhotic patients with SBP. IL-10 levels in the sera and ascitic fluids of studied groups were analyzed by ELISA and measured before and after treatment for SBP group. Results: SBP was common in males (68%) with mean age was (55.76±9.46 years). Serum and ascitic IL-10 levels were higher in SBP group than non SBP and control groups with mean value was (67.51±34.03 vs 26.50±13.03, 17.08±5.20 pg/ml respectively) in serum and (209±98.46 vs 86.01±37.69 pg/ml respectively) in ascitic fluid with highly statistically significant difference between groups (P=0.0001). Moreover, SBP group showed significant reduction in the levels of IL-10 in blood and ascitic fluid after treatment. Serum IL-10 at cut off value (35.86 pg/ml) had high sensitivity, specificity, PPV and NPV (88%, 80%, 84.6%, 84.2% respectively) with AUC was (0.924) and (p=0.0001) and ascitic IL10 at cut off value (99.75 pg/ml) had high sensitivity (80%) and low specificity (65%) with AUC was (0.874) and (P =0.0001). Conclusion: Serum IL-10 better than ascitic IL-10 in diagnosis of SBP, IL-10 levels in both serum and ascitic fluid may be related to clinical course of SBP.