The European red mite, Panonychus ulmi is one of the most important pests in the apple orchards. This species was introduced to Iran by apple seedlings from Europe. Apple growers often use several acaricides for the P. ulmi control. Abamectin and Fenpropathrin are an insecticide/acaricide which have been used extensively against P.ulmi in apple orchards. The aim of the present study was to study the evolution of abamectin and fenpropathrin resistance in field-collected populations of P. ulmi . Twelve strains of the ERMs were collected from commercial apple orchards of East Azarbaijan, West Azarbaijan, and Isfahan provinces in 2016 and 2017. Sequences of a part of the mitochondrial cytochrome oxidase subunit I (COI) gene were analyzed in seven Iranian P. ulmi populations. Comparison with available COI sequences in public databases (NCBI) identified all strains as P. ulmi. The acaricide toxicities on P. ulmi were determined by a leaf disc spray method using Potter spray tower.The LC 50 values to abamectin ranged from 1.39 mg a.i/l to 5.50 mg a.i/l, and field dose of abamectin is 3.6 mg a.i/L. Thus it seems that all sampled populations were possibly resistant to abamectin. The cytochrome P450 monooxygenase inhibitor PBO synergised abamectin toxicity in Shahin Dej (SR =2), Urmia (SR= 14), Mianeh1 (SR=15), Ahar (SR= 16) and Mahabad (SR=64). Pretreatment of TPP resulted in synergistic effects on abamectin toxicity in the Shahin Dej (SR=4.79) and Mahabad (SR=8.91) populations. The Glutathione S-transferase inhibitor DEM synergised abamectin in Shahin Dej population (SR= 2.33) and in Mahabad population (SR= 22.13). Therefore, resistance to abamectin is possibly polyfactorial in P.ulmi and the undertaken biochemical studies suggested the involvement of increased metabolic detoxication as major mechanism of resistance to abamectin. Toxicities of fenpropathrin and fenvalerate in different European red mite populations were also investigated. The Marnd (RR= 149), Maraqeh (RR=90) and Mianeh2 (RR=71) populations exhibited high levels of resistance to fenpropathrin, compared to the susceptible population (Shahin Dej). The Marand (RR= 21), Maraqeh (RR= 20), and Mianeh2 (RR= 19) was less sensitive to fenvalerate than the Shahin Dej Population. A positive cross resistance was observed between fenpropathrin and fenvalerate. Combined bioassays, synergistic and biochemical data indicated that target site insensitivity, mutations in voltage-gated sodium channels (VGSC), could be the major resistance component. By comparing partial VGSC sequences of field fenpropathrin-resistant (Marand, Maraqeh, and Mianeh2) and susceptible (Shahin Dej) populations, two point mutations, L1024V and F1538I were detected, which has been known to confer strong resistance to pyrethroids in mites. Keywords: European red mite,Resistance, Abamectin,Fenpropathrin,Mutation,F1538I, L1024V