Mesenchymal stem cells (MSCs) therapy is a promising treatment for Systemic lupus erythematosus (SLE) patients. However, this method is encumbered by suboptimal phenotype of MSCs used in clinical settings, and a short in vivo persistence time. Herein, inspired by the natural microstructure of the sand tower worm nest, we proposed novel adhesive porous particles with human MSCs encapsulation via microfluidic electrospray technology for SLE treatment. The porous microparticles were formed by immediate gelation reaction between sodium alginate (ALG) and poly-d-lysine (PDL), and then sacrificed polyethylene oxide (PEO) to form the pores. The resultant microparticles could protect MSCs from immune cells while maintain their immune modulating functions, and achieve rapid exchange of nutrients from the body. In addition, owing to the electrostatic adsorption and covalent bonding between PDL and tissues, the porous microparticles could adhere to the bowel surfaces tightly after intraperitoneal injection. Through in vivo imaging system (IVIS) methods and in vivo study, it was demonstrated that the MSCs-encapsulated porous adhesive microparticles could significantly increase the cellular half-life, turn activated inflammatory macrophages into an anti-inflammatory profile, and ameliorate disease progression in MRL/lpr mice. Thus, the MSCs-encapsulated porous microparticles showed distinctive functions in chronic SLE treatment, with additional potential to be used in a variety of biomedical applications.Keywords: Hydrogel; Mesenchymal stem cell; Microfluidics; Particle; Systemic lupus erythematosus.