The Asiatice stem borer, Chilo suppressalis (Walker), an important rice insect pest in China, has developed resistances to several classes of insecticides. To control C. suppressalis, chlorantraniliprole has been introduced as a novel insecticide in rice field since 2008. It is an anthranilic diamide insecticide that binds and activates ryanodine receptors (RyR). The susceptibility of field populations of C. suppressalis to chlorantraniliprole was determined in this study. The hypotheses of equality and parallelism showed that regression lines in the tested five populations were neither equal nor parallel. The Ruian, Cangnan, and Liangyungang populations (RA12, CN12, and LYG12) collected in 2012 had lower LD₅₀ values, whereas the Zhuji populations (ZJ12 and ZJ13) collected in 2012 and 2013 were ≈15 times more tolerant than the RA12 population. To determine the potential mechanisms involved in this tolerance variation, synergism bioassays were performed. Significant differences in susceptibility were found between without synergist and with synergist for the three populations (RA12, LYG12, and ZJ13), based on the tests for the hypotheses of equality. In RA12 and LYG12 populations with chlorantraniliprole, the addition of piperonyl butoxide (PBO) significantly synergized the activity, with synergism ratios of 2.68- and 2.33-fold, respectively, whereas addition of S,S,S-tributyl phosphorotrithioate (DEF) and diethyl maleate (DEM) had no synergist effect. In ZJ13 population with chlorantraniliprole, the addition of PBO and DEF increased synergism ratios by 12.43- and 6.31-fold, respectively, whereas addition of DEM had no significant effect on the toxicity against ZJ13 larvae. These susceptibility and synergism data suggested that detoxification enzymes might be involved in the tolerance variation to chlorantraniliprole in field populations of C. suppressalis.