A symbiotic fungi WFWML4 with acetylcholinesterase-inhibiting activity from Crassostrea rivularis was identified and its fermentation conditions were optimized.The strain was identified by both microscopic morphology and analysis of the nucleotide sequence of the 18 S rDNA.And fermentation medium,time,temperature,pH value,inoculum concentration,light period and culture volume were optimized to improve the inhibition activity of AChE in fermentation broth.Results showed the strain was confirmed as Chaetomium globosum,and the optimal fermentation conditions were as follows:SP medium was the suitable medium for the strain at pH 6.0.The light period was not a major factor during the AChE inhibitor production.The strain WFWML4 exhibited a higher AChE inhibitory activity68.07% ± 3.23% incubated with 10% inoculum and 200 mL /500 mL culture volume at 25℃ for 10 days.The symbiotic fungi from Crassostrea rivularis could be a new resource of anti-dementia substance.