Moringa oleifera decoction is used in folk medicine to alleviate various gastrointestinal ailments and has been shown in several studies to exhibit diverse biological activities: antioxidant, anti-inflammatory, and myorelaxant on intestine strips. However, its protective effect on pro-inflammatory cytokines in colitis remains to be ascertained. We investigated Moringa oleifera leaf aqueous extract activities on a rat model of acetic acid-induced colitis. Thirty-six rats were divided in random into six groups, and received either distilled water (10 mL/kg), the aqueous leaf extract of Moringa oleifera (25, 50, and 100 mg/kg) or the reference drug Loperamide (5 mg/kg) for 20 days. Animal body weight and food intake were followed-up. Colitis was induced on day 15, and daily stool weight was followed up. Animals were sacrificed (day 21), serum concentrations of pro-inflammatory cytokines MPO, IL-6, and TNF-α were evaluated, and the colon and liver preserved for histological examinations. After one-week pre-treatment, a significant (P < 0.05) weight increase was observed. At day 20, the extract significantly (P < 0.01) prevented weight loss. Food intake decreased by 36.33% in the colitis control, and by 4.34% in the extract (100 mg/kg) treated animals (P < 0.01). Moringa oleifera (100 mg/kg, day 20) decreased stool weights to 4.75±0.3 g (P < 0.05). The extract decreased (P < 0.01) MPO level. At 100 mg/kg, it significantly (P < 0.05) reduced IL-6 –0.58 ± 0.14 against 0.85 ± 0.00 ng/L in the colitis control. At the same dose, TNF-α levels decreased to 417.96 ± 0.17 ng/L (P < 0.001). Moringa oleifera alleviated colitis symptoms by reducing stool emission, alleviating inflammation, and preserving colon and liver cytoarchitecture.