Abstract: Objective To investigate the drug susceptibility trend of Salmonella paratyphi A (SPA) in Yuxi, Yunnan province, and provide evidence for the clinical use of antibiotics, patient treatment and eliminating infection source. Methods The K-B disk diffusion method was used to detect the drug susceptibility of 252 SPA isolates collected from 2005 to 2011 to 17 antibiotics. Furthermore, Etest test strip was used to test the minimum inhibitory concentration (MIC) of quinolones, including nalidixic acid, ciprofloxacin, levofloxacin and norfloxacin. Results The isolates were sensitive to ampicillin, amoxicillin, cephalothin, imipenem, netilmicin, sulfamethoxazole/trimethoprim and chloromycetin. The sensitive rate was 99.21% to cefotaxime, 98.41% to tetracycline, aztreonam and levofloxacin, 97.62% to nitrofurantoin, 95.63% to norfloxacin and 36.51% to ciprofloxacin. However, the sensitive rates to lomefloxacin and nalidixic acid were only 0.79%. All SPA isolates were resistant to rifampicin. The isolates’ intermediate rate to lomefloxacin declined with year, whereas the resistance rate increased with year. Moreover, the isolates’ intermediate rate to ciprofloxacin increased, but the sensitive rate decreased with year. Among 252 SPA isolates, 250 isolates were nalidixic acid resistant (NAR), the other 2 isolates were nalidixic acid sensitive (NAS). NAS isolates are more sensitive to the fluoroquinolones than NAR isolates, because the MICs of NAR isolates are much higher than those of NAS isolates (χ2=244.063,PConclusion Third generation cephalosporins could be used as the first choice in the treatment of Paratyphoid fever in Yuxi. The resistance of local SPA stains to fluoroquinolones is in increase, so the rational use of this antibiotic is important to stop the spread of their drug resistance.