Although rotenone is widely used as a pesticide, it has a low level of insecticidal activity on Spodoptera litura (F.) (Lepidoptera: Noctuidae). To gain a better understanding of the high tolerance to rotenone, a synergist (cinnamon oil) was added, and the comparative physiological impacts were assessed. After rotenone treatment, a considerable amount of rotenone was discharged in excreta, but extremely low levels were found in the ventral nerve cord and brain. By contrast, the rotenone cinnamon oil treatment group showed an increased amount of rotenone in the ventral nerve cord and brain. The co-toxicity coefficient for rotenone cinnamon was 213, indicating synergism. The midgut cells from insects treated with rotenone alone, and the controls, exhibited no significant differences, whereas those of the rotenone cinnamon oil group had larger intercellular spaces. These findings suggest that rotenone alone could not effectively penetrate the midgut, perhaps accounting for its low toxicity to S. litura. The rotenone cinnamon oil mixture apparently affected midgut cell spacing and membrane permeability, thus effectively increasing rotenone toxicity.