Adenosine deaminase 2 (ADA2) deficiency (DADA2) is a hereditary autoinflammatory disease for which no treatment has been established. The reason why exploration of pathogenesis and therapy for DADA2 are difficult is because mice, are often used as disease model animals, have not Cecr1 gene, encoding ADA2. While, zebrafish have two paralogs such as cecr1a and cecr1b, especially cecr1b is considered as DADA2 disease gene. This study aim was to develop the larval zebrafish model for DADA2 therapy. Cecr1b was knocked down (KD) with morpholino antisense oligonucleotide (MO), then cecr1b mRNA was significantly decreased compared with control. Cecr1b-KD zebrafish showed cerebral hemorrhage and motor dysfunction. Inflammatory cytokines have a possibility to be involved in vasculitis and cerebral hemorrhage in patients with ADA2 deficiency. Therefore, we investigated the effect of dimethyl fumarate (DMF), which has anti-inflammatory and antioxidant properties, on DADA2. DMF reduced the rate of cerebral hemorrhage and improved locomotor activity, and significantly decreased the mRNA levels of il-1β and il-6. These results suggest that cecr1b-KD zebrafish is a useful model for drug-evaluation system of DADA2 and DMF is a potential therapeutic agent for DADA2.