The aim of this study was to determine the sensitivity levels of 3 Neoseiulus californicus populations collected from the apple orchards located in Isparta province in 2012 to milbemectin by using spray tower-leaf disk method. The sensitivity of N. californicus populations to milbemectin were calculated by proportioning the LC50 levels of the field populations to that of the susceptible population. Moreover, the synergistic effects of the piperonyl butoxide (PBO), S-Benzyl-O,O-diisopropyl phosphorothioate (IBP) and diethylmaleate (DEM) synergists on milbemectin were determined. Resistance ratios of Egirdir, Eyupler and Gelendost populations were determined to be 7.20, 6.52 and 7.35 fold to milbemectin, respectively. The synergistic effects of PBO, IBP and DEM in Egirdir, Eyupler and Gelendost populations were found as <1, 1.59 and 1.85 fold; 1.81, 1.86 and 1.82 fold; 1.87, 1.52 and 2.25 fold, respectively. Enzymes of glutathione S-transferase (GST), monooxygenase (P450) and acetylcholinesterase (AChE) in N. californicus popluations were determined by using kinetic method; and the enzyme of esterase was determined by using the electrophoresis and kinetic methods. The enzyme levels of esterase, glutathion S-transferase (GST), monooxygenase (P450) and asetilkolinesterase (AChE) of N. californicus populations were changed from 8.86 to 11.64, 2.11 to 3.82, 0.02 to 0.05 and 0.01 to 0.02 mOD min(-1) mg(-1) proteins, respectively.