This study introduces the bio-inspired computation method namely Cuckoo Search (CS) as a parameter estimation method for modeling the mean activity coefficients of quaternary ammonium aqueous ionic liquids using the e-NRTL model. CS has not been used before to address this particular parameter estimation problem. Our calculations showed that the CS method was robust to perform the data modeling of this thermodynamic property of ionic liquids and that it can offer a global success rate of 90% for solving this challenging thermodynamic problem. CS offers a better performance than those obtained using other stochastic optimization methods such as simulated annealing, differential evolution, genetic algorithm or particle swarm optimization. This study highlights the capabilities of CS for facing challenging global optimization problems involved in the thermodynamic modeling of ionic liquids. We also show that the complexity of parameter estimation problems of ionic liquids appears to be determined by the type of cation and anion involved. Specially, the problems that involve ionic liquids containing [NH4+] and alkylsulfonates ions are more challenging. (C) 2014 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.