Robust artificial neural network (ANN) and fuzzy logic (FL) models were derived for chemical cleaning of microfiltration membranes fouled by milk under a wide range of operating conditions. The accuracies of the models were compared with multiple linear regressions (MLR). The developed models are useful tools for predicting the performance of chemical cleaning. The effects of different operating conditions on cleaning performance were elucidated using the ANN developed model. Moreover, optimum cleaning condition was determined by genetic algorithm and ANN model. The current research demonstrated that fuzzy logic and an artificial neural network can quantitatively capture cumulative effects of a range of operating conditions on flux recovery and resistance removal during a cleaning process.