The objective of this research study was to investigate and evaluate effects of bentonite on fatigue properties of hot mix asphalt (HMA) mixtures. The experimental program for this study included use of five percentages of bentonite (10%, 15%, 20%, 25% and 30%) by weight of bitumen for modifying base bitumen. Several tests such as: marshal stability, indirect tensile strength, resilient modulus and fatigue test were conducted. The fatigue tests were based on four-point bending test in strain controlled mode at 3microstrain levels (600-800-1000lm/m) with sinusoidal loading. The fatigue lives of mixtures have been evaluated based on the 50% reduction of the initial stiffness modulus. The results show that fatigue life of asphalt mixtures prepared with bentonite modified bitumen is longer than conventional HMAs. Also, bentonite leads to relative increase in indirect tensile strength and resilient modulus asphalt mixtures. Finally, based on experimental results, a model is proposed to describe the fatigue behavior of asphalt mixtures containing bentonite modified bitumen.