In vitro drug release rates from oil depot formulations intended for intra-articular injection have been investigated by using the rotating dialysis cell. The rate of drug appearance in the acceptor phase after instillation of sesame oil solutions of naproxen and lidocaine into the small aqueous donor compartment applied to first-order kinetics. In the present three-compartment model oil-aqueous phase distribution equilibrium was maintained at all times in the donor phase and thus drug efflux from the donor compartment was dictated by the distribution coefficient. A mathematical description of the rate of drug release into the acceptor phase and the interdependence of the observed apparent first-order rate constants and the drug oil-water distribution coefficients is provided. The in vitro model may constitute a valuable tool in formulation design and development allowing comparison of drug release rates originating from alteration of the oil vehicle composition, the drug compound or the composition of the release media to be performed.