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Background The purpose of the study was to investigate parents’ perceptions of antibiotic use for their children, interactions between parents and physicians regarding treatment with antibiotics, and factors associated with parents self-medicating children with antibiotics. Methods A cross-sectional study was conducted in vaccination clinics in two rural Chinese counties. Primary caregivers (the child’s parents in 97% of cases) visiting these clinics for the vaccination of their young children were given a 55-item structured questionnaire to collect information on the parents’ knowledge and attitudes regarding when, why, and how to use antibiotics and on their practices of purchasing antibiotics and medicating children. Results Of the 854 participating primary caregivers, 79% thought antibiotics could cure viral infections, and half believed that antibiotics could shorten the duration of upper respiratory tract infection. Parents reported a median of two hospital visits for their children during the previous 6 months, equal to the median number of antibiotic prescriptions received from physicians. Sixty-two percent of the parents had self-medicated their children with antibiotics. Living in rural villages (Adj OR = 1.643, 95% CI: 1.108–2.436), raising more than one child (Adj OR = 2.174, 95% CI: 1.485–3.183), increasing age of child (Adj OR = 1.146, 95% CI: 1.037–1.266), purchasing antibiotics without a prescription (Adj OR = 6.264, 95% CI: 4.144–9.469), storing antibiotics at home (Adj OR = 2.792, 95% CI: 1.961–3.975) and good adherence to physicians’ advice (Adj OR = 0.639, 95% CI: 0.451–0.906) were independently associated with self-medicating behavior. Conclusions Low levels of knowledge on the use of antibiotics and a high prevalence of self-medicating children with antibiotics were observed among parents in rural China. Interventions for the rational use of antibiotics in children should focus on strengthening mass health education, improving effective communication between physicians and patients, and enforcing supervision of the sale of antibiotics in retail pharmacies. [ABSTRACT FROM AUTHOR]