This study aimed to investigate the effect of inhibitors of the NF-kΒ alpha mutant gene (IkBaM) delivery to mensenchymal stem cells (MSCs) on rat chronic pancreatitis (CP). A total of 120 Sprague-Dawley rats were randomly divided into 6 groups of 20: Group A was injected with sterile saline solution, Group B was injected with allogenic MSCs, Group C1 was injected with allogenic IkBαM-MSCs cultured in vitro 4 h before CP modeling, Group C2 was injected with allogenic IkBαM-MSCs cultured in vitro during CP modeling, Group C3 was cultured with allogenic IkBαM-MSCs cultured in vitro 4 h after CP modeling, and Group D was injected with rAAV2-MSCs. Cytokine levels of ICAM-1, CTGF, IL-1, IL-6, IL-8, TNF-α, TIMP-1, TIMP-2, IL-10, FN, MMP-1, MMP-2, MMP-3, and MMP-9 were examined. The results indicated that allogenic IκBαM-MSCs could reduce pro-inflammatory cytokine levels and increase anti-inflammatory cytokine levels in CP. The allogenic IkBαM-MSCs reduced the activation and promoted the apoptosis of pancreatic stellate cells in the rat model of CP. IkBαM-MSCs influenced the proliferation and apoptosis of pancreatic stellate cells by regulating the activation of the PPAR, MAPK, mTOR, TGF-β, NOD-like receptor, Notch, WNT, TGF-β1-SMAD-2/3, and P53 signal transduction pathways.