Objective To retrospectively analyze pathogen distribution, antimicrobial resistance, and their changing trends in patients with infectious endophthalmitis admitted to a hospital in Xingtai area during the past 10 years. Methods Patients with infectious endophthalmitis and were detected pathogens admitted to Hebei Eye Hospital from January 2014 to December 2023 were selected for a retrospective study. Culture results and antimicrobial resistance of pathogens from patients with endophthalmitis were summarized and analyzed. The mutation characteristics of resistance genes and cassette chromosome recombinase genes in methicillin-resistant Staphylococcus epidermidis (MRSE) strains were explored. In vitro virulence between MRSE strains carrying mutant and non-mutant genes was compared using serum killing test. Results A total of 671 patients (671 eyes) with infectious endophthalmitis were included in the study, with 484 pathogenic strains (from 484 eyes) isolated. The average age of patients was (65.66±25.14) years old. There were no statistically significant differences in the constituent rates of pathogens among infectious endophthalmitis patients of different genders and ages (both P>0.05). Incidence of infectious endophthalmitis was higher in summer and lower in winter. Except 2018, there were statistically significant differences in the constituent rate of infectious endophthalmitis among different seasons from 2016 to 2023 (all P<0.05). A total of 176 strains of Staphylococcus epidermidis, 81 strains of Streptococcus, and 48 strains of Pseudomonas aeruginosa were isolated. The resistance rates of Staphylococcus epidermidis to penicillin, erythromycin, and oxacillin were all over 40%, with a resistance rate of 64.20% to penicillin. From 2019 to 2023, the resistance rates of Staphylococcus epidermidis to penicillin, erythromycin, oxacillin, compound sulfamethoxazole, and ciprofloxacin were all higher than those from 2014 to 2018, and the differences were all statistically significant (all P<0.05). The resistance rates of Streptococcus to azithromycin, erythromycin, and clindamycin were all over 80%. The resistance rate of Pseudomonas aeruginosa to both ciprofloxacin and piperacillin exceeded 70%. Among the 113 MRSE strains, the resistance genes ermA, ermB, and ermC accounted for 12.39% (n=14), 13.27% (n=15), and 74.34% (n=84), respectively. The cassette chromosome recombinase genes mainly included ccrA1-ccrB1, ccrA2-ccrB2, and ccrA3-ccrB3 types. Gene mutations were detected from all three types of resistance genes, with a mutation rate of 81.42% (92/113). The colony count of antimicrobial-resistant gene-mutated Staphylococcus epidermidis was higher than that of non-mutated strains in serum killing test at 2 and 3 hours (both P<0.05). Conclusion The constituent rates of pathogens in infectious endophthalmitis remained stable over the 10 years, with the highest proportion in summer and the lowest in winter. The detection rate of antimicrobial-resistant pathogens presented rising tendency, and the resistance gene of MRSE was mainly ermC. Testing and monitoring of MRSE strains should be strengthened in clinic to prevent the cloning and spread of resistance genes.