Objective: To clarify the distribution of asthma in preschool children aged 3-6 years old and the protective effect of breastfeeding on asthma in three provinces in the middle and lower reaches of the Yangtze river in China. Methods: The parents of 27 200 preschoolers chosen from kindergartens in 11 cities of Hubei, Jiangsu and Anhui Province were investigated with children’s asthma and breastfeeding during October to November in 2017. Results: The asthma detection rate for preschoolers was 4.0%,5.0% for boys and 2.9% for girls. The asthma detection rate for children aged 3,4,5,and 6 years old was 3.2%,3.7%,4.4%,and 4.9%. 3 448 (12.7%) and 7 630 (28.1%) preschoolers were never breastfed or mainly breastfed. The rate of exclusive breastfeeding was 50.0% for 1 to 5 months and only 10.2% over 6 months. Meanwhile,there was a significant protective effect on asthma (OR=0.88,95%CI=0.77-0.89) by exclusive breastfeeding for 1-5 months,which was still statistically significant after adjusting for confounding factors. After adjusting for confounding factors,exclusive breastfeeding over 6 month have significant effected on preschool children aged 4 years old without allergic conjunctivitis history (OR=0.63,95%CI=0.40-0.99). Furthermore,exclusive breastfeeding over 6 month had important effect on preschool children aged 4 years old with eczema history (OR=0.52,95%CI=0.27-0.99). Conclusion Exclusive breastfeeding has protective effect on asthma in preschool children. Exclusive breastfeeding over 6 months even has better protective effect on asthma for the 4-years-old children without the history of allergic conjunctivitis and eczema.