The present study investigated the feasibility of ostrich oil utilizing as a promising vehicle for improved skin permeation of sinomenine with reference to vaseline matrix containing different content of chemical enhancers. The fatty acid composition of ostrich oil was analyzed by GC-MS. Penetration enhancing potential of ostrich oil on permeation of sinomenine across rat abdominal skin in vitro was studied using an automatic diffusion cell apparatus. The content of sinomenine percutaneous absorbed was determined by HPLC. Various parameters viz. steady-state skin flux (J(ss)), permeability coefficient (kP), cumulative amount of sinomenine (Q) and enhancement ratios (ER) were calculated from the permeation data. Fick's law of diffusion and Scheuplein kinetic were used to evaluate the transdermal absorbent enhancement of ostrich oil to sinomenine. Ostrich oil showed significant penetration effect on sinomenine compared with vaseline matrix containing different content of chemical enhancers, the density sequence as follow: 2% Azone > ostrich oil > 1% Azone plus 1% propylene glycol > 1% Azone > 3% Azone > 1% propylene glycol. The percutaneous endosmic rate constant (J(ss)) and permeability coefficient (k(P)) of sinomenine in ostrich oil through rat skin were 10.01 μg/cm²/h and 0.087, respectively. Ostrich oil produced stronger enhancement (ER = 24.31) with greater cumulative amount of drug permeated (255.53 μg/cm²) up to 24 h and caused no skin irritation. The drug release of sinomenine was coincided with Fick's equation. In summary, ostrich oil containing fatty acids is proposed as a promising adjuvant for use in cosmetics and pharmaceuticals for improved permeation of drug.