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Background: Erythropoietin (EPO) promotes myelination and functional recovery in rodent peripheral nerve injury (PNI). While EPO receptors (EpoR) are present in Schwann cells, the role of EpoR in PNI recovery is unknown because of the lack of EpoR antagonists or Schwann cell‐specific EpoR knockout animals. Methods: Using the Cre‐loxP system, we developed a myelin protein zero (Mpz) promoter‐driven knockout mouse model of Schwann cell EpoR (MpzCre‐EpoRflox/flox, Mpz‐EpoR‐KO). Mpz‐EpoR‐KO and control mice were assigned to sciatic nerve crush injury followed by EPO treatment. Results: EPO treatment significantly accelerated functional recovery in control mice in contrast to significantly reduced functional recovery in Mpz‐EpoR‐KO mice. Significant muscle atrophy was found in the injured hindlimb of EPO‐treated Mpz‐EpoR‐KO mice but not in EPO‐treated control mice. Conclusions: These preliminary findings provide direct evidence for an obligatory role of Schwann‐cell specific EpoR for EPO‐induced functional recovery and muscle atrophy following PNI. [ABSTRACT FROM AUTHOR]