Here, we reported an over-activation of APLN/APJ axis in T2DM patients’ testis using single-cell RNA sequencing technology, we aim to use both in and ex vivo systems to explore the role of APLN/APJ in impairing normal spermatogenesis under hyperglycemic conditions, and whether targeting APLN/APJ serves as a promising strategy to improve spermatogenesis for diabetic patients. The gene discussed is APLNR; the disease is type 2 diabetes mellitus.