Degradation of native kappa-carrageenan was performed using acid hydrolysis aided with microwave heating. Combined with nonofiltration membrane (cut-off molecular weight 250 Da) separation, 1. 400 Da - 50 kDa low-molecular-weight (LMW) kappa-carrageenans were obtained. Narrow molecular weight distribution of LMW kappa-carrageenans could be prepared under pH 2.18 during the microwave power range investigated. The in vivo anti-influenza virus (IV) activity of three kinds of LMW kappa-carrageenans (3, 5, and 10 kDa), their acetylated derivatives (acetylation degree of 1.5), as well as an acetylated and sulfated derivative of 3 kDa carrageenan (acetylation degree of 1.0 and sulfation degree of 2.4), were investigated using FM1-induced pulmonary oedema model. These LMW kappa-carrageenans showed significant inhibition against FM1-induced pulmonary oedema as compared with the virus control, although their activities were inferior to that of positive control, Rabivirin. Introduction of acetyl groups greatly increased their anti-IV activity. The acetylated 3-kDa kappa-carrageenan exhibited comparative activity with Rabivirin at both doses of 6 and 30 2. mg/kg center dot d, and the acetylated and sulfated derivative of 3 kDa carrageenan displayed higher activity than Rabivirin at the dose of 30 mg/kg center dot d. These results disclosed that 3 kDa kappa-carrageenan with proper acetylation degree and sulfation degree was a potential candidate against influenza virus. (C) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013