Our　previous　study　has　demonstrated　that　Pseudostellaria　heterophylla　protein　hydrolysate　(PPH)　has　immunomodulatory　activity　on　murine　spleen　lymphocytes.　The　aim　of　this　study　was　to　investigate　the　excitation　of　PPH　in　RAW264.7　macrophage　cells　and　the　protective　effect　in　cyclophosphamide　(CTX)-treated　mice.　The　results　showed　PPH　of　50　μg/mL　could　stimulate　macrophages　resulting　in　significant　promotions　of　nitric　oxide　(NO)　production,　endocytosis　and　reactive　oxygen　species　formation.　Meanwhile,　enzyme-linked　immunosorbent　assay　(ELISA)　revealed　that　the　levels　of　tumor　necrosis　factor-α　and　interleukin-10　were　significantly　upregulated　by　PPH.　Furthermore,　50　mg/kg　per　day　PPH　restored　the　T　lymphocyte　proliferation　and　natural　killer　cell　activity,　and　increased　NO　production　and　pinocytosis　of　peritoneal　macrophages　in　CTX-treated　mice.　These　findings　indicate　PPH　plays　a　crucial　role　in　RAW264.7　macrophage　cells　activation　and　in　the　protection　against　immunosuppression　in　CTX-treated　mice　and　could　be　used　as　a　potential　immunostimulant　agent.　©　2019　Elsevier　Ltd