Stem bark extract of Alstonia boonei (SBEAB) was reported to possess anti-lipidemia, anti-microbial, antiinflammatory and anti-hypercholesterolemia properties in folk lore medicine. The present study examined the effects of SBEAB on some key lipid profiles in diabetic induced rats. Biomarkers of lipid damage, histological and immunohistochemical method were used. The expression level of cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) were also determined. SBEAB administered orally at dose of 200 mg/kg for 14 days significantly lowered the levels of cholesterol, triglyceride and malondialdehyde induced by single intraperitoneal administration of streptozotoxin (STREP) (80 mg/kg) and preserved the integrity of intestinal villi. In addition, SBEAB reduced the STREP-induced elevated activity of CAT with concomitant repression of COX-2 and iNOS expression in the intestine of diabetic rats. The protective effect of SBEAB was compared to that of metaglomide (METAG), anti-diabetic drug. Pre and post-treatment are better to prevent pro-inflammatory response and intestinal cancer in diabetic rats than METAG-administration. Taken together, the inhibition of genes programming COX-2 and iNOS expression suggest the molecular mechanism for small intestinal tract protection by SBEAB and further advocates the links between the mal-absorption of cholesterol in diabetic patients.