Chemical modifications of polysaccharides can provide an opportunity to obtain new agents with possible therapeutic uses. In this study, a water-soluble polysaccharide extracted from Loquat Leaves (coded LLPs) was purified by the column chromatography, which was used to investigate its acetylation process by the acetic anhydride method. The Degree of Substitution (DS) was used as the index, the effect of acetylated reagent amounts, reaction temperature and reaction time on DS was investigated. Acetylation process of LLPs was optimized by Response Surface Methodology (RSM) coupled with Box-Behnken design based on the results of single factor experiments. Characterization and antioxidant activities of Acetylated LLPs (Ac-LLPs) were investigated. Results showed that the optimal acetylation process of LLPs was obtained as following: Acetylated reagent amounts 2.60 mL, reaction time 2.10 h, reaction temperature 31℃. Under the optimal acetylation process, the maximum DS was 0.3570. Moreover, the analysis of Fourier-Transform Infrared spectroscopy (FT-IR) confirmed that the structural modification of Ac-LLPs was successful. In addition, the antioxidant activities assay in vitro suggested that Ac-LLPs possessed better DPPH radical scavenging capacity and stronger hydroxyl radical scavenging capacity compared with LLPs, whereas the scavenging capacity of LLPs on superoxide anion radical was slightly higher than Ac-LLPs. The results indicated that Ac-LLPs had enormous potential to become a new food additive or antioxidant supplement in food and pharmaceutical industries.