It　is　unknown　whether　a　scaffold　containing　both　small　intestinal　submucosa　(SIS)　and　mesenchymal　stem　cells　(MSCs)　for　transplantation　may　improve　pancreatic　islet　function　and　survival.　In　this　study,　we　examined　the　effects　of　a　SIS-MSC　scaffold　on　islet　function　and　survival　in　vitro　and　in　vivo.　MSCs　and　pancreatic　islets　were　isolated　from　Sprague-Dawley　rats,　and　SIS　was　isolated　from　Bamei　pigs.　The　islets　were　apportioned　among　3　experimental　groups　as　follows:　SIS-islets,　SIS-MSC-islets　and　control-islets.　In　vitro,　islet　function　was　measured　by　a　glucose-stimulated　insulin　secretion　test;　cytokines　in　cultured　supernatants　were　assessed　by　enzyme-linked　immunosorbent　assay;　and　gene　expression　was　analyzed　by　reverse　transcription-quantitative　PCR.　In　vivo,　islet　transplantation　was　performed　in　rats,　and　graft　function　and　survival　were　monitored　by　measuring　the　blood　glucose　levels.　In　vitro,　the　SIS-MSC　scaffold　was　associated　with　improved　islet　viability　and　enhanced　insulin　secretion　compared　with　the　controls,　as　well　as　with　the　increased　the　expression　of　insulin　1　(Ins1),　pancreatic　and　duodenal　homeobox　1　(Pdx1),　platelet　endothelial　cell　adhesion　molecule　1　[Pecam1;　also　known　as　cluster　of　differentiation　31　(CD31)]　and　vascular　endothelial　growth　factor　A　(Vegfa)　in　the　islets,　increased　growth　factor　secretion,　and　decreased　tumor　necrosis　factor　(TNF)　secretion.　In　vivo,　the　SIS-MSC　scaffold　was　associated　with　improved　islet　function　and　graft　survival　compared　with　the　SIS　and　control　groups.　On　the　whole,　our　findings　demonstrate　that　the　SIS-MSC　scaffold　significantly　improved　pancreatic　islet　function　and　survival　in　vitro　and　in　vivo.　This　improvement　may　be　associated　with　the　upregulation　of　insulin　expression,　the　improvement　of　islet　microcirculation　and　the　secretion　of　cytokines.