Abstract: Objective: To study the curing process of health meal replacement powder (HMR) and evaluate its anti-depression function. Methods: The mixed traditional Chinese medicine powder of HMR was cured by stewing, stir-frying, microwave and other processes. Meanwhile, the physicochemical indexes, total polysaccharides, total flavonoids and characteristics in vitro digestive were determined. The depression model mice were established by intraperitoneal injection of LPS, and mice were randomly divided into blank control group, model control group, fluoxetine hydrochloride group and HMR group. Using the tail suspension test and forced swimming test in mice, the antidepressant effect of HMR was observed. The behavior, IL-1β, TNF-α, 5-HT, NE and BDNF of mice were determined. Results: After curing, the water solubility index (WSI), water absorption index (WAI), centrifugal sediment rate (SR), dispersibility time, wettability time, total polysaccharide and total flavonoids content of extrusion group were 34.35%, 3.18 g/g, 52.16%, 184.12 s, 195.02 s, 32.2 mg/g and 0.62 mg/g. The results showed that extrusion could not improve the soakage and disperal of Chinese medicine powder as much as other curing processes like baking, but it could significantly increase the content of soluble small molecules and active substances of Chinese medicine powder. Results of in vitro digestion showed that extrusion had a little effect on the release of total flavonoids from Chinese medicine powder, but the content of rapidly digestible starch (RDS) (63.52%) was lower, and the content of slowly digestible starch (SDS) (34.14%) was significantly higher than that of other groups (P<0.05). The results of animal experiments showed that compared with the model control group, HMR group could significantly reduce the resting time of tail suspension and swimming, down-regulate the levels of IL-1β and TNF-α, up-regulate the levels of 5-HT and NE, and increase the contents of BDNF (P<0.01). Conclusion: The physicochemical indexes of extrusion process sample meet the good nutrient absorbability requirements of products, and its functional components increase greatly, the extrusion sample was slow GI and health regimen. Therefore, extrusion is the best curing process to prepare HMR. HMR can significantly improve the depression-like behavior and indexes of depressive model mice.