In this paper, we demonstrate, for the first time, how an external osmotic gradient can be used to regulate diffusion of solutes across a lipid membrane. We present experimental and theoretical studies of the transport of different solutes across a monoolein membrane in the presence of an external osmotic gradient. The osmotic gradient introduces phase transformations in the membrane, and it causes nonlinear transport behavior. The external gradient can thus act as a kind of switch for diffusive transport in the skin and in controlled release drug formulations.