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The objective of this study was to formulate a self‐nanoemulsifying oral drug delivery system (SNEDDS) for the poorly water‐soluble trans‐Cinnamic acid (t‐CA SNEDDS) that could be evaluated for its antihyperglycemic efficacy in comparison to the parent t‐CA in an alloxan‐induced diabetic rat model. A SNEDDS formulation consisting of 60% surfactant (Kolliphor EL), 10% co‐surfactant (PEG 400) and 30% oil (isopropyl myristate) proved to be optimal. t‐CA SNEDDS (80 mg/kg, p.o.), t‐CA suspension (80 mg/kg, p.o.), and Metformin Hydrochloride Tablets (230 mg/kg, p.o.) were administer qdfor 30 days to diabetic rats. After treatment the body weight of diabetic rats was increased, blood glucose levels, total cholesterol, and triglyceride in the serum tended to be normalized, while the levels of alanine aminotransferase and aspartate aminotransferase were markedly decreased. The effects of t‐CA SNEDDS were superior to that of the t‐CA suspension. The present study demonstrated that t‐CA was effective in attenuating the effects of alloxan treatment and that t‐CA SNEDDS with a more favorable absorption and enhanced bioavailability is more effective than t‐CA. Drug Dev Res 76 : 8282–93, 2015. © 2015 Wiley Periodicals, Inc.

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