A numerical study has been performed on the heat transfer mechanism of Newtonian and non-Newtonian fluids in 2 : 1 horizontal rectangular ducts. The effects of temperature dependence of viscosity, shear thinning, and buoyancy-induced secondary flow are all considered. Experimental data for Newtonian fluid, water, and non-Newtonian fluid, Separan AP-273 solution (0.1%), were chosen for the comparison with the numerical results. For water, the present numerical results are all in good agreement with the experimental data. The heat transfer enhancement is caused by the buoyancy-induced secondary flow. For Separan AP-273 solution (0.1%), the present numerical results agree with the experimental data in the region near the entrance, but the present modeling underestimates the value of Nu in the fully-developed region. In the region near the entrance, the heat transfer enhancement is caused mainly by the axial velocity distortion, which is mainly due to the temperature dependence of viscosity. The effect of buoyancy-induced secondary flow are much weaker in the case for Separan solution rather than that for water. It is mainly caused by the relatively high viscosity of fluid around the central zone of rectangular duct.