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Background: We investigated the anti- inflammatory effect of type II cannabinoid receptor (CB 2 receptor) activation and their relationship to iron influx on 1-methyl-4-phenylpyridinium (MPP + ) treated astrocytes., Methods and Results: By western blots, real-time PCR and ELISA, the expressions of CB2 receptor, divalent metal transporter-1 (DMT1), cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), interleukin-1β (IL-1β) and tumor necrosis factor- α (TNF-α) were measured. Iron influx into astrocytes was determined by the quenching of calcein fluorescence. We found that pre-treatment with JWH133, a selective CB 2 receptor agonist, significantly suppressed the MPP + -induced up-regulation of COX-2, iNOS, IL- 1β and TNF-α in astrocytes. In addition, JWH133 significantly inhibited the MPP + -induced up- regulation of DMT1. Further studies indicated that JWH133 suppressed the MPP + -accelerated iron influx into astrocytes. These effects were blocked by co-treatment with AM630, the CB 2 receptor antagonist., Conclusions: These results suggest that activation of CB 2 receptor inhibit MPP + -induced inflammatory response and iron influx in astrocytes., (Copyright © 2020 Elsevier B.V. All rights reserved.)