The objective of this study is to investigate the beneficial effects and underlying mechanism of dietary -mannanase supplementation on the productive performance of laying hens fed with metabolic energy (ME)reduced diets. A total of 448 Hy-Line gray laying hens were randomly assigned to seven groups. Each group had 8 replicates with 8 hens. The groups included a control diet (CON) with a ME of 2750 kcal/Kg, diets reduced by 100 kcal/Kg or 200 kcal/Kg ME (ME_100 or ME_200), and diets with 0.15 g/Kg or 0.2 g/Kg -mannanase (ME_100+ -M_0.15, ME_100+ -M_0.2, ME_200+ -M_0.15, and ME_200+ -M_0.2). The productive performance, egg quality, intestinal morphology, inflammatory response, mRNA expression related to the Nuclear factor kappa B (NF-kB) and AMPK pathway, and cecum microbiome were evaluated in this study. ME-reduced diets negatively impacted the productive performance of laying hens. However, supplementation with-mannanase improved FCR, decreased ADFI, and restored average egg weight to the level of the CON group. ME-reduced diets increased the levels of interleukin-1 (IL -1b) and IL -6 while decreasing the levels of IL -4 and IL -10 in the jejunum of laying hens. However, dietary-mannanase supplementation improved jejunum morphology, reduced pro-inflammatory cytokine concentrations, and increased levels of anti-inflammatory factors in laying hens fed with ME-reduced diets. The mRNA levels of IL -6, IFN-g, TLR4, MyD88, and NF-kB in the jejunum of ME-reduced diets were significantly higher than that in CON, dietary -mannanase supplementation decreased these genes expression in laying hens fed with ME-reduced diets. Moreover, dietary -mannanase supplementation also decreased the mRNA levels of AMPKa and AMPKg, and increased the abundance of mTOR in the jejunum of laying hens fed with ME-reduced diets. Cecum microbiota analysis revealed that dietary -mannanase increased the abundance of various beneficial bacteria (e.g., g_Pseudoflavonifractor, g_Butyricicoccus, and f_Lactobacillaceae) in laying hens fed with MEreduced diets. In conclusion, dietary -mannanase supplementation could improve the productive performance of laying hens fed with a ME-reduced diet by improving intestinal morphology, alleviating intestinal inflammation, changing energy metabolism-related signaling pathways, and increasing cecum-beneficial microbiota.