In this study heat transfer and fluid flow characteristics of Al2O3/water nanofluid in a serpentine microchannel is numerically investigated. A constant heat flux is applied on microchannel wall and a single-phase model has been adopted using temperature-dependent properties. The effects of pertinent factors such as Reynolds number (Re=10, 20, 50 and 100), particle volume fraction (𝛷=0(distilled water), 2, 4 and 8%) and heat flux (q=5, 10 and 15 W/cm2), on the velocity and temperature field, average heat transfer coefficient (havg), pressure drop (Δp), and thermal-hydraulic performance (η) are evaluated. The results show that the use of nanofluid causes increased velocity gradient near the wall which is more remarkable for φ = 8%. The results also reveal that the heat transfer rate increases as nanoparticle volume fraction and Reynold number increase and a maximum value 51% in the average heat transfer coefficient is detected among all the considered cases when compared to basefluid (i.e., water). It is found that a higher heat flux leads to heat transfer enhancement and reduction in pressure drop. Finally, thermal-hydraulic performance is calculated and it is seen that the best performance occurs for Re =10 and φ = 4%.