The tomato leaf minor ( Tuta absoluta Meyrick) (Lepidoptera: Gelechiidae) is one of the most important pests of tomato in world and Iran. Due to significant resistance of this pest against insecticides, principles of resistance management must be considered in pesticides application. In this study, resistance of different populations of the tomato leaf minor from Isfahan province was evaluated against abamectin and cypermethrin. The median lethal concentration (LC 50 ) of different populations were measured by bioassays using a leaf-dip method. The LC 50 of abamectin in the reference population of Isfahan University of Technology (IUT) was estimated as 5.67 mg a.i/L, while the population of Shahre-e-Abrisham1 showed a 25-fold resistance, with on LC 50 value of 143.18 mg a.i/L. Other treated populations showed also 2- to 20-fold resistance to abamectin. Pre-treatment of different populations with DEM synergist, on inhibitor of glutathione-s-transferases (GSTs), increased 2.7- to 5.9-fold of the toxicity of abamectin. GST activity was significantly different between resistant and reference populations. TPP, on inhibitor of esterases (ESTs), increased abamctin toxicity in the populations as much as 2.5- to 3.7-fold. The activity of ESTs in these populations was also significantly different. Furthermore, inhibiting of cytochrome P450 monooxygenases by PBO, increased abamectin toxicity about 3-fold in the population of Shahre-e-Abrisham1. It seems that GSTs and ESTs play a more important role in the resistance development against abamectin in the studied populations. Also, the zymograms for ESTs have proved their role in abamectin resistance. Against cypermethrin a tested populations showed an LC 95 4600 mg a.i/L, while recommended dose of this insecticide is about 30 mg a.i/L. PBO pre-treatment reduced LC 50 of cypermethrin more than TPP and DEM. The synergistic ratios of PBO for the reference population of IUT, and Mourche Khort population were 2.16 and 3.51, respectively. The activities of cytochrome P450 monooxygenases in Falavarjan and Mourche khort populations were evaluated 2 and 1.26 times higher than that of IUT population, respectively. DEM synergist increased cypermethrin toxicity in the resistant population of Kondelan 3.67-fold, while in IUT population 2-fold synergistic ratio was observed. Also, enhanced activity of GSTs in resistant populations was possibly associated with resistance to cypermethrin. In addition, increased cypermethrin toxicity after inhibiting the activity of ESTs by TPP was not significant between tested populations. Evaluating the activity of ESTs in the reference and resistant populations did not show any significant difference. Therefore, it could be concluded that cytochrome P450 monooxygenase and GST enzymes play a minor role in resistance of cypermethrin, but the main resistance mechanism possibly was associated with mutations in the pest sodium channel gene. High levels of resistance to abamectin and cypermethrin in the collected populations from Isfahan province shows the importance of insecticide resistance management based on alternative use of insecticides with different mode of action or chemical group. Keywords : Enzyme activity, Synergist, Insecticide resistance management