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The world of Mushihimesama takes place within Shinju forest, which is ruled by large arthropods known as the Koujuu. Their life essence known as "Levi Sense", is poisonous to human beings and thus humans live in the shadows of these gigantic beasts. According to an agreement with the Koujuu, some humans are allowed to live in small villages if they offer a sacrifice of a 15 year old once every 200 years. At the start of Mushihimesama, the time for this sacrifice is drawing near.
Reco was born to royalty within Hoshifuri Village, one of the small settlements following the agreement with the Koujuu. When she was a young child, Reco became lost in the Shinju forest, outside of the village. There, she met a young boy named Aki who was wearing a golden bracelet. Upon mentioning how beautiful the bracelet was, Aki gave it to her and showed her the way back to Hoshifuri.. The bracelet provided to Reco gave her a telepathic link with the Koujuu, allowing her to speak with and understand them. As she grew up, Reco befriended the beetle Kiniro and often played in the Shinju Forest, a place where no other villagers dared venture.
The people of her village were terrified, since they recognized the bracelet as being an item given to the designated sacrifices. When Reco turned 15, everyone in the village became sick and began to die except for her. Her father told her to visit the god of the Koujuu and Reco embarked on her mission with Kiniro, resulting in the events of Mushihimesama.
After some travel, Reco discovers that the king of the Koujuu is Aki and is forced to face him in combat. Upon victory, Aki tells Reco that on the day they had met, he sensed she had been poisoned by Levi Sense. The bracelet he had given her was crystallized Levi Sense and saved her life (in addition to the telepathic power she received) . A mortally wounded Aki passes his role of protecting the forest on to Reco and passes away in a cloud of Levi Sense, promising to protect her in spirit. It turns out that the village sacrifices are not killed, but rather bestowed the role of guardian of the forest, with Aki presumably being the sacrifice from 200 years prior. In killing Aki, Hoshifuri village returned to normal.
This leads into the events of the 2nd game in the series: Mushihimesama Futari. Aki's mother Larsa, the queen of another small village is enraged when she learns of Aki's death at the hands of Reco. She sends her youngest son Palm to interrogate and kill Reco and avenge her oldest and favorite son. When Palm finally does encounter Reco, he realizes that although she did kill Aki, she was trying to help her village and Aki wished for events to transpire as they did. They both head back to Larsa to explain what had happened, but Larsa is blinded by her wish to avenge her son and attacks regardless. Upon defeating Larsa, Reco goes back to Shinju Forest as its guardian with Kiniro.