In this article electrokinetic mixing through heterogeneous microchannels has been studied and the effects of slip coefficient, zeta-potential, Debye–Hückel parameter and Reynolds number on mixing efficiency have been investigated. The microchannels studied here, have non-homogenous zeta-potential distribution at the wall, while other surface properties are considered to be homogenous. In order to investigate the electro-osmotic mixing, the Navier–Stokes, Nernst–Planck, Laplace and convection–diffusion equations have been solved numerically for velocity field, ions distribution, electrical potential and concentration field, respectively. The entropy of concentration distribution has been used as a quantitative index to evaluate the mixing performance. The results show that the behavior of electro-osmotic micromixers strongly depends on the amount and distribution of wall zeta-potential and in most cases the mixing efficiency increases with reduction of slip coefficient or Debye–Hückel or Reynolds number. It is found that in presence of slip, mixing efficiency decreases at low Reynolds numbers, while increases at high Reynolds numbers. Also, the accuracy of Helmholtz–Smoluchowski approximate model is investigated and it is found that the performance of the Helmholtz–Smoluchowski model in predicting the mixing efficiencies deteriorates for high wall zeta-potential or low values of Debye–Hückel parameter.