Objective To explore the possible mechanism of Xiaoke Formula（消渴方） for type 2 diabetes mellitus（T2 DM）. Methods High-fat and high-sugar feed combined with intraperitoneal injection of 35 mg/kg 2% streptozotocin-citrate buffer were used to establish the T2 DM rat model. Forty successfully modeled rats were randomly divided into model group

inhibitor group

Xiaoke Formula group

Xiaoke Formula plus inhibitor group（combination group）

with 10 rats in each group; and another 10 SD rats were set as the normal group. After modeling

rats in the Xiaoke Formula group were given 17 g/（kg·d） Xiaoke Formula by gavage; the inhibitor group was given tail vein injection of 0.5 mg/（kg·d） VIVIT peptide; the combination group received both Xiaoke Formula and VIVIT with the same dose and administration way as other groups; the model group and the normal group were administered with 1.9 ml normal saline by gavage. Five weeks later

levels of fasting blood glucose（FBG）

fasting insulin（FINS）

glycosylated serum protein（GSP）

calcium ion(Ca

2+

) and calcineurin（CaN） in the pancreatic tissue were detected; HE staining was used to observe the pathological changes of pancreatic islets; the protein expression of insulin and nuclear factor of activated T cell c1（NFATc1） in the pancreatic tissue

as well as the mRNA expression of neurogenin 3（Ngn3） and pancreaticoduodenal homeobox factor 1（PDX-1） were detected. Results Compared to those of the normal group

the FBG and GSP levels of the model group significantly increased

and the expressions of FINS

CaN

Ca

2+

NFATc1

Ngn3 mRNA and PDX-1 mRNA were all decreased（P

<

0.01）. HE staining showed that the cells number of the pancreatic islets was significantly reduced

the shape was irregular

and the interstitium increased; certain islet tissue structures was even completely shrinked and disintegrated. Compared to the model group

Xiaoke Formula group showed better effects on all the outcome measurements（P

<

0.01）. HE staining showed that the number of islets increased significantly

and were distributed in complete clumps with richer cytoplasm. Compared to the Xiaoke Formula group

the combination group had increased levels of FBG and GSP

and decreased expression of FINS

CaN

Ca

2+

NFATc1

Ngn3 mRNA

and PDX-1 mRNA（P

<

0.05 or P

<

0.01）. Conclusion Xiaoke Formula can regulate blood sugar and protect pancreatic β-cells

the mechanism of which may be related to the regulation of the Ca

2+

/CaN/NFAT signaling pathway in pancreatic tissue and the increase of β-cell regeneration-related transcription factors.