In the present research, experimental study and artificial neural network (ANN) modeling were performed to analyze and estimate the friction factor (f) in serpentine microchannels. Three serpentine microchannels with various geometric parameters used in the experiments with a hydraulic diameter of 800 mu m, different ratios of straight length to hydraulic diameter (L-S/D-h), and different curvature ratios (R-C/D-h). The computational fluid dynamic (CFD) simulation was employed and the results were compared with the experimental data. After validation, the CFD modeling was used to study more cases with different geometrical parameters. The numerical-validated data was applied as input data set of the ANN model. Reynolds number (Re), L-S/D-h and R-C/D-h were considered as input variables of the ANN model and f was determined as the target data. The validity of this model was evaluated through one-third of all of data points, which were not used in the training of the network. Furthermore, an empirical correlation for prediction off was developed in the form of classical power-law correlation and the equation constants were determined using genetic algorithm (GA) technique. (c) 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.