Structural evolution and mechanical properties of polyurethane/epoxy interpenetration networks (PU/EP IPNs) as a function of PU content were comprehensively studied. In particular, tribological behaviors of the IPNs were investigated in water medium while varying lubrication regimes. Our results demonstrate that microstructures of PU/EP IPNs are closely dependent on stoichiometric proportions of their components. It is impressive that unlike conventionally modified polymers, blending 30wt% PU into EP leads to simultaneous improvement in modulus, strength and ductility. Especially for sliding subjected to boundary lubrication, IPNs exhibited strikingly enhanced tribological performance when compared to neat EP and PU. Our work indicates that IPNs have a high application potential as tribo-materials exposed to water lubrication.