This study was conducted to determine the antibiotic and screening resistance genes of Escherichia coli (E. coli) isolated from diarrheal yak calves from high remote plateau in Sichuan, China. A total 41 rectal swabs were obtained from diarrheal yak calves. E. coli were isolated and identified. The antimicrobial sensitivity was tested by piloting the disk diffusion method for 21 antibiotics. Polymerase chain reaction was employed to detect the resistance genes. The results showed that the drug resistance ranged from 2.4% (amikacin) to 53.7% (tetracycline), while no isolates were found resistant to neomycin and polymyxin B. Multi-drug resistance was detected in 4.9% isolates to 17 antimicrobial agents; and 24.4% isolates were found susceptible to all antimicrobial agents. The aminoglycoside resistance genes of aac(3)-lla, ant(3')-la and aph(3')-lla was positive in 4.9%, 2.1% and 7.3% E. coli isolates respectively. The 4.9% and 2.1% of E. coli isolates were detected in b-Lactam resistance genes of TEM and CTX-M, respectively; and 12.2% and 4.9% of E. coli isolates were found to have Tetracycline resistance genes of tetM and tetA, respectively. The present study reveals that the yak calves from high cold plateau are potential reservoir of E. coli with widely distributed multiple drug resistance which requires the attention of concerned authorities regarding the use of non-standard antibiotics.