Objective To analyze the characteristics of drug resistance to quinolones and erythromycin of clinical Campylobacter jejuni (C .jejuni) strains and to further investigate its molecular mechanisms .Methods A total of 193 clinical C .jejuni strains were isolated from feces of patients with diarrhea .Drug susceptibilities to ciprofloxacin (CIP ) , gentamycin (GEN ) , azithromycin (AZI ) , erythromycin (ERY) ,chloromycetin (CHL) ,doxycycline (DOX) and tetracycline (TET) were tested using standard agar dilution method . gyrA , gyrB and parC genes were amplified by polymerase chain reaction (RCR) and analyzed for molecular mechanisms of quinolones resistance ,and 23S rRNA , rplD and rplV genes for erythromycin resistance .Chi‐square test or Fisher′s exact two‐tailed tests were used to perform the statistical analysis .Results A total of 193 clinical C . jejuni strains were isolated during 1994—2010 ,among which 43 C .jejuni strains were isolated in 1994—1999 ,80 in 2000—2005 and 70 in 2006—2010 .The drug resistance rates for CIP increased significantly from 55 .8% in 1994—1999 to 95 .0% in 2000—2005 and 94 .3% in 2005—2010 (χ2=41 .94 ,P<0 .01) .The drug resistance rates for GEN were 0 in 1994—1999 ,11 .3% in 2000—2005 and 10 .0% in 2006—2010 ,but with no statistic difference (χ2=5 .078 , P=0 .08) .The drug resistance rates for AZI were 0 in 1994—1999 ,3 .8% in 2000—2005 and 4 .3% in 2006—2010 (χ2=1 .81 ,P=0 .40) .The drug resistance rates for ERY were 0 in 1994—1999 ,1 .3% in 2000—2005 and 4 .3% in 2006—2010 (χ2 = 2 .87 , P= 0 .24 ) . T he drug resistance rates for CHL were 2 .3% in 1994—1999 ,11 .3% in 2000—2005 and 20 .0% in 2006—2010 (χ2 =7 .82 ,P=0 .02) .The drug resistance rates for DOX were 60 .5% in 1994‐1999 ,86 .3% in 2000—2005 and 82 .9% in 2006—2010 (χ2 =12 .18 ,P<0 .01) .The drug resistance rates for TET were 74 .4%in 1994—1999 ,95 .0% in 2000—2005 and 94 .3% in 2006—2010 (χ2 = 15 .46 , P< 0 .01 ) .T he drug resistance rates for CIP‐DOX‐TET were 37 .2% in 1994—1999 ,83 .8% in 2000—2005 and 80 .0% in 2006—2010 (χ2 =33 .53 ,P<0 .01) .The drug resistance rates for CHL‐CIP‐DOX‐TET were 0 in 1994—1999 ,7 .5% in 2000—2005 and 20 .0% in 2006—2010 (χ2=12 .68 ,P<0 .01) .The drug resistance rates for GEN‐CIP‐DOX‐TET were 0 in 1994—1999 ,7 .5% in 2000—2005 and 8 .6% in 2006—2010 (χ2 =3 .74 ,P=0 .15) .All 163 CIP‐resistant C .jejuni strains had C257T mutation on gyrA gene .Mutations on gyrB gene were silent .ParC gene was absent in C .jejuni .Four ERY resistant C .jejuni strains had no mutation on rplD and rplV genes , but 3 of them had A2075G mutation on 23S rRNA gene . Conclusions The antimicrobial resistance rates for C .jejuni increase remarkably over the periods .C257T mutation on gyrA gene and A2075G mutation on 23S rRNA gene are main mechanisms for quinolones resistance and erythromycin resistance ,respectively .