Tire microplastics (TMPs) are ubiquitous in terrestrial environments and affect many soil-dwelling species like the earthworm Eisenia fetida. In this study, the enzymatic activity catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx), and glutathione S-transferase (GST) of adult (0.3-0.5 g) E. fetida was assessed after 14 days of exposure to four TMP levels: 10, 50, 100, and 200 mg TMP/g artificial soil. Using the ANOVA and Dunnett's post hoc tests, significant increases were observed in the activity of CAT, SOD, GPx, and GST between the control (10.3, 242.7, 39.3, and 13.0 nmol/min/ml, respectively) and test groups (17.7, 331.0, 1.9, and 16.4 nmol/min/ml, respectively) while the MDA activity remained statistically similar among the experiments. The most remarkable changes were identified in the activity of SOD and GPx where the difference between the control and test groups became significant at all TMP concentration levels. Particularly, the E. fetida exposure to 100 and 200 mg/g TMP significantly (p value < 0.05) increased the activity of CAT, SOD, GPx, and GST, suggesting that the species immune system is stimulated via the production of hydrogen peroxide.